De novo DNA methylation independent establishment of maternal imprint on X chromosome in mouse oocytes.
In female mouse embryos, the paternal X chromosome (Xp) is preferentially inactivated during preimplantation development and trophoblast differentiation. This imprinted X-chromosome inactivation (XCI) is partly due to an activating imprint on the maternal X chromosome (Xm), which is set during oocyte growth. However, the nature of this imprint is unknown. DNA methylation is one candidate, and therefore we examined whether disruptions of the two de novo DNA methyltransferases in growing oocytes affect imprinted XCI. We found that accumulation of histone H3 lysine-27 trimethylation, a hallmark of XCI, occurs normally on the Xp, and not on the Xm, in female blastocysts developed from the mutant oocytes. Furthermore, the allelic expression patterns of X-linked genes including Xist and Tsix were unchanged in preimplantation embryos and also in the trophoblast. These results show that a maternal disruption of the DNA methyltransferases has no effect on imprinted XCI and argue that de novo DNA methylation is dispensable for Xm imprinting. This underscores the difference between imprinted XCI and autosomal imprinting.
Chiba
Hatsune
H
Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, 1111 Yata, Mishima, Japan.
Hirasawa
Ryutaro
R
Kaneda
Masahiro
M
Amakawa
Yuko
Y
Li
En
E
Sado
Takashi
T
Sasaki
Hiroyuki
H
D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D009865:Oocytes / Q000502:physiology*; D019076:Transgenes / Q000235:genetics; D014327:Trophoblasts / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism*
C000717967:DNMT3A protein, human; D006657:Histones; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D008239:Lysine